Abstracts

Rationale: A drug-induced hyperammonemic encephalopathy has been well-known to occur following administration of valproate. The development of this condition has only rarely been described following administration of topiramate and valproate in combination. Methods: We describe a case of an acute hyperammonemic encephalopathy secondary to administration of topiramate and valproate in an adult admitted to a University Hospital for treatment of recurrent seizures. Results: A 53-year old female with a history of recurrent meningiomas and complex partial seizures presented with seizures and altered mentation. Medications at admission included phenytoin and levetiracetam. Clinical and electrographic evidence pointed to a diagnosis of complex partial status epilepticus. Topiramate and valproate were added to the patient’s anti-epileptic regimen due to lack of response to previous anti-epileptic drugs. Seizures were subsequently controlled and the patient briefly returned to her baseline cognitive level. Five days later, the patient was noted to become progressively lethargic. Serum ammonia level was 94 um/L (normal = 11 - 45). Liver and renal function tests were within normal limits. Serum valproate levels were within therapeutic range. Work-up for infectious and other metabolic causes of encephalopathy was negative. Video-electroencephalography showed marked generalized background slowing consistent with a metabolic encephalopathy without any clinical or electrographic seizures. Neuroimaging did not reveal any lesions to explain her sudden cognitive decline. The patient was treated with enteral lactulose in an intensive care setting. Topiramate and valproate were rapidly weaned. Carnitine levels (total, free, esterified, esterified to free ratio) were within normal limits. The patient returned to her baseline mental status four days later with normalization of serum ammonia level. She was discharged from the hospital with no further sequelae. Conclusions: This is one of the few reported cases of an acute hyperammonemic encephalopathy secondary to the combined use of topiramate and valproate. Salient features include excessive somnolence, elevation of serum ammonia level up to twice normal laboratory values and generalized background slowing on electroencephalography without epileptiform changes. Although the pathophysiology is not completely understood, a synergistic effect of topiramate and valproate on hepatic and renal metabolism is thought to cause the hyperammonemia. The condition is reversible with discontinuation of topiramate, valproate or both. Oral lactulose may be beneficial in some cases. The role of carnitine metabolism and replacement therapy is not well understood in this situation. Early identification and treatment of this condition is essential in reducing morbidity.